Metabolomic analysis reveals the changing trend and differential markers of volatile and nonvolatile components of Artemisiae argyi with different aging years.

INTRODUCTION: Artemisia argyi Folium (AAF) is a traditional medicinal herb and edible plant. Analyzing the differential metabolites that affect the efficacy of AAF with different aging years is necessary. OBJECTIVE: The aim of the study was to investigate the changing trend and differential markers of volatile and nonvolatile metabolites of AAF from different aging years, which are necessary for application in clinical medicine. METHODOLOGY: Metabolites were analyzed using a widely targeted metabolomic approach based on ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and gas chromatography tandem mass spectrometry (GC-MS). RESULTS: A total of 153 volatile metabolites and 159 nonvolatile metabolites were identified. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) could clearly distinguish AAF aged for 1 year (AF-1), 3 years (AF-3), and 5 years (AF-5). Seven flavonoids and nine terpenoids were identified as biomarkers for tracking the aging years. CONCLUSIONS: The metabolomic method provided an effective strategy for tracking and identifying biomarkers of AAF from different aging years. This study laid the foundation for analysis of the biological activity of Artemisia argyi with different aging years.

The Browning Properties, Antioxidant Activity, and α-Glucosidase Inhibitory Improvement of Aged Oranges (Citrus sinensis).

Oranges contain many natural active chemicals, organic acids, and polysaccharides. Aging processing is commonly used to modify the color, quality, functional components, and stability of fruits. This study assesses the preparation of aging black oranges using various pre-treatments and solid fermentation. Oranges were aged for six weeks in fresh, non-blanching, blanching, and hot air-assisted aging cycle (AA) groups. The oranges' shrinkage ratio, color difference values, and soluble solids content changed significantly (p < 0.05). Principal component analysis indicated that aging fermentation treatment accelerated glycolysis and increased the ratio of reducing sugars. The enhanced browning can be associated with the oxidation of ascorbic acid (0.66-0.47 mg/g) and the formation of 5-hydroxymethylfurfural (5-HMF) (0.09 mg/g). Furthermore, the presence of free polyphenols led to an increase in the total polyphenol and total flavonoid content. It also had a synergistic effect with 5-HMF in increasing the 2,2-diphenyl-1-picrylhydrazyl free radical-scavenging capacity and ferric ion-reducing antioxidant power (p < 0.05). AA had superior α-glucosidase inhibitory ability increasing from 67.31 to 80.48%. It also reduced the development time by 33%. Therefore, aging technology can enhance the bioactive compounds in oranges and provide a reference for future whole-fruit aging fermentation and health product creation.

Utilizing Extracellular Vesicles for Eliminating 'Unwanted Molecules': Harnessing Nature's Structures in Modern Therapeutic Strategies.

Extracellular vesicles (EVs) are small phospholipid bilayer-bond structures released by diverse cell types into the extracellular environment, maintaining homeostasis of the cell by balancing cellular stress. This article provides a comprehensive overview of extracellular vesicles, their heterogeneity, and diversified roles in cellular processes, emphasizing their importance in the elimination of unwanted molecules. They play a role in regulating oxidative stress, particularly by discarding oxidized toxic molecules. Furthermore, endoplasmic reticulum stress induces the release of EVs, contributing to distinct results, including autophagy or ER stress transmission to following cells. ER stress-induced autophagy is a part of unfolded protein response (UPR) and protects cells from ER stress-related apoptosis. Mitochondrial-derived vesicles (MDVs) also play a role in maintaining homeostasis, as they carry damaged mitochondrial components, thereby preventing inflammation. Moreover, EVs partake in regulating aging-related processes, and therefore they can potentially play a crucial role in anti-aging therapies, including the treatment of age-related diseases such as Alzheimer's disease or cardiovascular conditions. Overall, the purpose of this article is to provide a better understanding of EVs as significant mediators in both physiological and pathological processes, and to shed light on their potential for therapeutic interventions targeting EV-mediated pathways in various pathological conditions, with an emphasis on age-related diseases.

Efficient Tin-Lead Perovskite Solar Cells with a Ultrawide Usage Windows of Precursor Solution Opened by SnF2.

High quality tin-lead perovskite solar cells (Sn─Pb PSCs) can be fabricated via simple solution processing methods. However, the instability of precursor solutions and their narrow usage windows still pose challenges in manufacturing efficient and reproducible Sn─Pb PSCs, hindering the commercialization of PSCs. Fluorine tin (SnF2 ) is widely used as an antioxidant to improve the crystallinity of perovskite. In this study, another role of SnF2 as a stabilizer is found to restrain the deprotonation of methylammonium iodide (MAI) in the precursor solution, which improves their stability and expands their usage windows. Due to the inhibition of SnF2 on oxidation and deprotonation, stable large-sized colloidal clusters form gradually in perovskite precursor solution during aging, leading to uniform nucleation/crystallization during film growth, significantly reducing the roughness and defect density in the films. Because of the competitive deprotonation and oxidation process of Sn2+ , the benefit of larger cluster maximizes after about ten days storage of precursor solution. The champion efficiency of Sn─Pb PSCs prepared with 10 days aged precursor solution is 22.00%. High performance of devices fabricated with precursor solution stored for even ≈40 days discloses the wide usage windows of precursor solution with SnF2 additive.

The Anatomical Layering Assessment: The Construction of Beauty.

Restructuring an aging face from bone structure to the surface of the skin can be metaphorically compared to building and renovating a house. While each anatomical layer of the face undergoes an aging process of its own, there is also an interdependency of superficial structures on deeper layers, so that a change in one layer may lead to changes to the adjacent layers. This interaction among the structures deep into the skin, along with the skin's ability to envelope them is what determine the aspect of the aging face. Thus, a careful assessment of all the layers is imperative and we describe herein a step-by-step facial layering assessment and facial restructuring approach from bone structure to the surface of the skin to implement a treatment plan able to deliver a harmonious rejuvenating outcome.

The aging trajectories of brain functional hierarchy and its impact on cognition across the adult lifespan.

Introduction: The hierarchical network architecture of the human brain, pivotal to cognition and behavior, can be explored via gradient analysis using restingstate functional MRI data. Although it has been employed to understand brain development and disorders, the impact of aging on this hierarchical architecture and its link to cognitive decline remains elusive. Methods: This study utilized resting-state functional MRI data from 350 healthy adults (aged 20-85) to investigate the functional hierarchical network using connectome gradient analysis with a cross-age sliding window approach. Gradient-related metrics were estimated and correlated with age to evaluate trajectory of gradient changes across lifespan. Results: The principal gradient (unimodal-to-transmodal) demonstrated a significant non-linear relationship with age, whereas the secondary gradient (visual-to-somatomotor) showed a simple linear decreasing pattern. Among the principal gradient, significant age-related changes were observed in the somatomotor, dorsal attention, limbic and default mode networks. The changes in the gradient scores of both the somatomotor and frontal-parietal networks were associated with greater working memory and visuospatial ability. Gender differences were found in global gradient metrics and gradient scores of somatomotor and default mode networks in the principal gradient, with no interaction with age effect. Discussion: Our study delves into the aging trajectories of functional connectome gradient and its cognitive impact across the adult lifespan, providing insights for future research into the biological underpinnings of brain function and pathological models of atypical aging processes.

Flavor characterization of Citri Reticulatae Pericarpium (Citrus reticulata 'Chachiensis') with different aging years via sensory and metabolomic approaches.

Guangchenpi (GCP), which is the peel of Citrus reticulata 'Chachiensis', is widely used as an herbal medicine, tea and food ingredient in southeast Asia. Prolonging its aging process results in a more pleasant flavor and increases its profitability. Through the integration of sensory evaluation with flavoromic analysis approaches, we evaluated the correlation between the flavor attributes and the profiles of the volatiles and flavonoids of GCP with various aging years. Notably, d-limonene, γ-terpinene, dimethyl anthranilate and α-phellandrene were the characteristic aroma compounds of GCP. Besides, α-phellandrene and nonanal were decisive for consumers' perception of GCP aging time due to changes of their odor activity values (OAVs). The flavor attributes of GCP tea liquid enhanced with the extension of aging time, and limonene-1,2-diol was identified as an important flavor enhancer. Combined with machine learning models, key flavor-related metabolites could be developed as efficient biomarkers for aging years to prevent GCP adulteration.

A quality comparison for Xiecun Huangjiu with different aging stages based on chemical profile, aroma composition and microbial succession.

The Xiecun Huangjiu (XCHJ), an exemplary representation of North Huangjiu, exhibits a distinct and invigorating aroma predominantly formed during its aging period. In this study, we observed dynamic changes in 16 key aroma compounds by gas chromatography-mass spectrometry (GC-MS) during the aging of XCHJ, with compounds such as phenethylalcohol, isoamylalcohol, benzaldehyde, and ethylbenzoate initially increasing and then decreasing. Ultra-Performance Liquid Chromatography (UPLC) detected nineteen amino acids, with total content ranging from 1901.45 to 3764.45 mg/L. High-throughput sequencing indicated that Pseudomonas, Ochrobactrum, Moesziomyces and Aspergillus et al. were abundant in aged XCHJ. Totally, 4 bacteria and 8 fungi exhibited strong associations with aroma compounds production. Physicochemical properties were primarily interacted with Pseudomonas, Aspergillus, Pseudeurotium, Thermomyces, Bacteroides and Blautia. Furthermore, co-occurrence network analysis highlighted significant interactions between Pantoea, Rhodotorula, Monascus, and amino acids. These findings provide valuable insights for the regulation of aroma in aged XCHJ.

Study of changes in the aging process, microstructure, and mechanical properties of AA2024-AA1050 nanocomposites created by the accumulative roll bonding process, with the addition of 0.005 vol.% of alumina nanoparticles.

We created AA2024-AA1050 and AA2024-AA1050/0.005 vol.% Al2O3 nanocomposites by six accumulative roll bonding (ARB) process cycles. We used AA2024 and AA1050 sheets with a thickness of 0.7 mm and plate-shaped alumina nanoparticles to create a composite. The two AA1050 and one AA2024 sheets (among the two AA1050 sheets) were ARB-ed up to six cycles with and without adding alumina nanoparticles. Also, a sample of the AA1050 without composite making was ARB-ed up to six cycles. We aged some composites after the ARB process in the furnace at 110, 150, and 190 °C. This project performed SEM, TEM, and EDS-MAP analyses, tensile strength, microhardness, and Pin-on-Disc tests to study the ARB-ed sheets. The results of the tensile tests showed that the tensile strength of AA2024-AA1050 created by the six cycles ARB process was two times more than primary AA1050. Also, the wear resistance of this composite was 74% more than six cycles ARB-ed the AA1050. Using 0.005 vol.% alumina nanoparticles in AA2024-AA1050 composite improved its wear resistance by 30%. In the following, the aging process caused an improvement in tensile strength and total elongation of AA2024-AA1050/Al2O3 nanocomposites.

How soon do metabolic alterations and oxidative distress precede the reduction of muscle mass and strength in Wistar rats in aging process?

Here we investigate metabolic changes, the antioxidant system and the accumulation of oxidative damage in muscles with different fiber types during the aging process in Wistar rats and try to map how sooner the changes occur. To do so, 30 male Wistar rats were submitted to behavioral evaluation to determine voluntary strength in the 11, 15, and 19 month old rats, measuring the energy metabolism, antioxidant system, oxidative damage and structure in the soleus and extensor digitorum longus muscles. We detected structural and metabolic changes in both muscles, especially in the EDL of 15 month old rats and in the soleus of 19 month old rats. In the 15 month old rats, there was a reduction in the cross-sectional area of the fibers, and a reduction in the proportion of type I fibers, accompanied by an increase in fiber density and the amount of type IIA fibers. This change in the fiber profile was followed by an increase in the activity of anaerobic metabolism enzymes, suggesting a reduction in the oxidative capacity of the muscle. In addition, there was an increase in the rate of lipid peroxidation, accompanied by a reduced antioxidant capacity. In the 19 month old rats, these disturbances got stronger. In summary, the present study demonstrated that before functional disturbances, there was an accumulation of oxidative damage and structural changes in the skeletal muscle beginning at 15 months old in the EDL and the soleus only in the biochemical parameters. Therefore, the metabolic alterations occurred at 15 months old and not before.

Influence of aging process and restoration thickness on the fracture resistance of provisional crowns: A comparative study.

Background: The advancement of digital dentistry enhanced the fabrication of indirect provisional restorations utilizing durable materials, yet the performance of provisional crowns fabricated with various techniques, and different thickness remains unknown. Thus, this in-vitro study aimed to evaluate the influence of restoration thickness and aging on the fracture behavior of provisional crowns fabricated using different techniques. Methods: A dentiform maxillary first molar was prepared using a highly filled epoxy resin material to construct identical die replicas. Four groups of provisional crowns were fabricated: Group 1 was milled at 1.5 mm occlusal thickness; Group 2 was milled at 0.9 mm thickness; Group 3 was 3D-printed at 1.5 mm occlusal thickness; and Group 4 was 3D-printed at 0.9 mm occlusal thickness. Eight crowns from each group were subjected to a thermocycling process for 5000 cycles between baths held at 5 °C and 55 °C with a dwell time of 30 s and transfer time of 5 s. All crowns (aged and non-aged (control)) were loaded for fracturing using a universal testing machine at a 0.5 mm/min crosshead speed. Data were analyzed using a two-way analysis of variance and multiple comparisons at (α = 0.05). Results: The maximum mean force load was found in the non-aged milled group (M1.5) at 1706.36 ± 124.07 N; the minimum mean force load was recorded for the aged 3D-printed group (3D0.9) at 552.49 ± 173.46 N. A significant difference was observed before and after thermocycling (p < 0.01). Conclusion: Computer-aided design and manufacture of milled provisional crowns is superior to 3D-printed crowns for fracture resistance.

Exogenous Klotho Extends Survival in COVID-19 Model Mice.

A striking feature of COVID-19 disease is the broad spectrum of risk factors associated with case severity, as well as the diversity of clinical manifestations. While no central agent has been able to explain the pathogenesis of SARS-CoV-2 infection, the factors that most robustly correlate with severity are risk factors linked to aging. Low serum levels of Klotho, an anti-aging protein, strongly correlate with the pathogenesis of the same risk factors and manifestations of conditions similar to those expressed in severe COVID-19 cases. The current manuscript presents original research on the effects of the exogenous application of Klotho, an anti-aging protein, in COVID-19 model mice. Klotho supplementation resulted in a statistically significant survival benefit in parametric and non-parametric models. Further research is required to elucidate the mechanistic role Klotho plays in COVID-19 pathogenesis as well as the possible modulation SARS-CoV-2 may have on the biological aging process.

Microbial, Physicochemical Profile and Sensory Perception of Dry-Aged Beef Quality: A Preliminary Portuguese Contribution to the Validation of the Dry Aging Process.

Beef dry-aging consists of a selection of unpackaged prime cuts placed in a controlled environment cold room for several weeks. The goals are to concentrate flavors like nutty and beefy and to improve tenderness. The aim of this study was to verify the microbiological and physicochemical behavior and sensory perception of meat during a sample process example of meat dry-aging. Twelve beef loins were selected for 90 days of dry aging and placed in a cold room with average temperature, relative humidity and forced air 3.2 ± 0.7 °C, 60.7 ± 4.2% and 0.5-2 m/s, respectively. Samples of crust and lean meat were collected on days 1, 14, 21, 35, 60 and 90 of the dry aging process for microbiological, physicochemical (pH, aw, color L*a*b*) and sensory analysis. During drying, no pathogenic bacteria were detected, and the average counts were higher for the crust. The average values for water activity (aw) and pH were 0.98 ± 0.02 and 5.77 ± 0.015, respectively. A slight decrease in aw and an increase in pH were observed over the aging period (p < 0.05). The lower microbial counts on the lean meat and the overall assessment of freshness confirm the importance of good manufacturing and storage practices during dry aging.

Active aging and urban policies: the space as an instrument for an inclusive and sustainable city.

Aging is one of the most important challenges of our times. As stated by United Nations' report on 1983, "Policies to meet the challenge of a growing, healthier and more active seniors population -based on the view of the ageing of society as an opportunity to be utilized -automatically benefit the individual ageing person, materially and otherwise. Similarly, any effort to ameliorate the quality of life for the seniors, and to meet their diverse social and cultural needs, enhances their capacity to continue interacting with society". Aging society provides not only a new context, but a new opportunity to rethink our traditional views of age. The growing number of seniors people will soon make the majority of overall population. As noticed by reports of international organizations, cities will play a more important role in dealing with these quantitative and cultural changes, mostly because it is expected that a quarter of the population over 60 will be concentrating in the central areas of compact cities. In brief, cities are at once growing and aging at an incredible speed. Although aging process represents a fundamental and structural phenomenon with very deep consequences at economic, social and political level, and with an impact on the individual one as on the society as whole, our cities should deal with this process and respond, in terms of public health and social care, to needs of older people, also those that will experience a loss of autonomy. It is important to note that there are a greater heterogeneity within older population in terms of conditions and demands, which depend on their specific personal, social and familial context. Urban space - in its complex differentiation between public space, third space, and private space - represents both a tool and a strategic factor in pursuing the objective of ensuring high levels of widespread well-being and, from a political perspective, fully shaping the right to the city for seniors individuals.

What matters in aging is signaling for responsiveness.

Biological responsiveness refers to the capacity of living organisms to adapt to changes in both their internal and external environments through physiological and behavioral mechanisms. One of the prominent aspects of aging is the decline in this responsiveness, which can lead to a deterioration in the processes required for maintenance, survival, and growth. The vital link between physiological responsiveness and the essential life processes lies within the signaling systems. To devise effective strategies for controlling the aging process, a comprehensive reevaluation of this connecting loop is imperative. This review aims to explore the impact of aging on signaling systems responsible for responsiveness and introduce a novel perspective on intervening in the aging process by restoring the compromised responsiveness. These innovative mechanistic approaches for modulating altered responsiveness hold the potential to illuminate the development of action plans aimed at controlling the aging process and treating age-related disorders.

Determination of key factors affecting biofilm formation on the aged Poly(ethylene terephthalate) during anaerobic digestion.

Biofilm formation on plastic surface is a growing concern because it can alter the plastic surface properties and exacerbate the ecological risk. Identifying key factors that affecting biofilm formation is critical for effective pollution control. In this study, the poly (ethylene terephthalate) (PET) was aged in water and air conditions with UV irradiation, then incubated in the digestate of food waste anaerobic digestion to allow biofilm formation. Surface analysis techniques, including scanning electron microscopy (SEM), atomic force microscopy (AFM), and Fourier-transform infrared spectroscopy with attenuated total reflection (FTIR-ATR), were utilized to investigated the changes in the topography, roughness, hydrophily, and functional groups change of the PET surface during the aging process. Confocal laser scanning microscopy (CLSM) was used to determine the distribution of microorganisms on the PET surface after incubation in the digestate. This study focused on understanding the interactions between the PET surface and biofilm to identify critical surface factors that affect biofilm formation. Results showed that the four months aging process decreased the contact angle of the PET surface from 96.92° to 76.08° and 68.97° in water and air conditions, respectively, corresponding to an increase of 44% and 70% in the surface energy. Additionally, aging in air conditions led to a rougher surface compared to water conditions. The arithmetic roughness average (Ra) of the PET-Water was 11.0 nm, comparable to that of the pristine PET, while the value of PET-Air was much higher (43.9 nm). The results further indicated that biofilm formation during anaerobic digestion was more sensitive to roughness than hydrophily. The PET surface aged in air conditions provided a more suitable environment for microbial reproduction, leading to the aggradation of living cells.

Exploring the roles of microorganisms and metabolites in the 30-year aging process of the dried pericarps of Citrus reticulata 'Chachi' based on high-throughput sequencing and comparative metabolomics.

GuangChenpi (GCP), the dried pericarps of Citrus reticulata 'Chachi', has been consumed daily as a food and dietary supplement in China for centuries. Its health benefits are generally recognized to be dependent on storage time. However, the specific roles of microorganisms and metabolites during long-term storage are still unclear. In this study, comparative metabolomics and high-throughput sequencing techniques were used to investigate the effects of co-existing microorganisms on the metabolites in GCP stored from 1 to 30 years. In total, 386 metabolites were identified and characterized. Most compounds were flavonoids (37%), followed by phenolic acids (20%). Seventeen differentially upregulated metabolites were identified as potential key metabolites in GCP, and 8 of them were screened out as key active ingredients by Venn diagram comparative analyses and verified by network pharmacology and molecular docking. In addition, long-term storage could promote the accumulation of secondary metabolites. Regarding the GCP microbiota, Xeromyces dominated the whole 30-year aging process.Moreover, Spearman correlation analysis indicated that Bacillus thuringiensis and Xeromyces bisporus, the dominant bacterial and fungal species, were strongly associated with the key active metabolites. Our results suggested that the change of active ingredients caused by the dominant microbial is one of the mechanisms affecting the GCP aging process. Our study provides novel functional insights and research perspectives on microorganism-associated metabolite changes that may improve the GCP aging process.

Impact of air pollution on cardiovascular aging.

The world population is aging rapidly, and by some estimates, the number of people older than 60 will double in the next 30 years. With the increase in life expectancy, adverse effects of environmental exposures start playing a more prominent role in human health. Air pollution is now widely considered the most detrimental of all environmental risk factors, with some studies estimating that almost 20% of all deaths globally could be attributed to poor air quality. Cardiovascular diseases are the leading cause of death worldwide and will continue to account for the most significant percentage of non-communicable disease burden. Cardiovascular aging with defined pathomechanisms is a major trigger of cardiovascular disease in old age. Effects of environmental risk factors on cardiovascular aging should be considered in order to increase the health span and reduce the burden of cardiovascular disease in older populations. In this review, we explore the effects of air pollution on cardiovascular aging, from the molecular mechanisms to cardiovascular manifestations of aging and, finally, the age-related cardiovascular outcomes. We also explore the distinction between the effects of air pollution on healthy aging and disease progression. Future efforts should focus on extending the health span rather than the lifespan.

Characterizing emission factors and oxidative potential of motorcycle emissions in a real-world tunnel environment.

Transportation emissions significantly affect human health, air quality, and climate in urban areas. This study conducted experiments in an urban tunnel in Taipei, Taiwan, to characterize vehicle emissions under real driving conditions, providing emission factors of PM2.5, eBC, CO, and CO2. By applying multiple linear regression, it derives individual emission factors for heavy-duty vehicles (HDVs), light-duty vehicles (LDVs), and motorcycles (MCs). Additionally, the oxidative potential using dithiothreitol assay (OPDTT) was established to understand PM2.5 toxicity. Results showed HDVs dominated PM2.5 and eBC concentrations, while LDVs and MCs influenced CO and CO2 levels. The CO emission factor for transportation inside the tunnel was found to be higher than those in previous studies, likely owing to the increased fraction of MCs, which generally emit higher CO levels. Among the three vehicle types, HDVs exhibited the highest PM2.5 and eBC emission factors, while CO and CO2 levels were relatively higher for LDVs and MCs. The OPDTTm demonstrated that fresh traffic emissions were less toxic than aged aerosols, but higher OPDTTv indicated the impact on human health cannot be ignored. This study updates emission factors for various vehicle types, aiding in accurate assessment of transportation emissions' effects on air quality and human health, and providing a guideline for formulating mitigation strategies.

Effects of Testosterone Replacement Therapy on Muscle Strength in Older Men with Low to Low-Normal Testosterone Levels: A Systematic Review and Meta-Analysis.

BACKGROUND: Previous studies and meta-analyses have explored the relationship among testosterone, muscle strength, and physical function, to the best of our knowledge, no meta-analysis has investigated the effects of testosterone replacement therapy (TRT) on subgroup of relatively hypogonadal older men. OBJECTIVE: The aim of this study was to evaluate the effect of TRT in older men with low testosterone levels. METHODS: PubMed, Embase, and Web of Science were systematically searched for articles published between January 1990 and April 2020. We included randomized controlled studies that investigated the effect of TRT and included older men (age >60 years) with relatively low testosterone levels. Studies were extracted following the PRISMA flowchart, and the included randomized controlled trials were evaluated using RoB 2.0. Our main outcome was muscle strength changes after TRT evaluated using a metaregression of confounding factors. Secondary outcomes included changes in physical performance and the risk ratio of adverse events. Random-effects meta-analyses of TRT on muscle strength and physical function were performed. RESULTS: Thirteen studies with 2,043 patients were included. The mean age of subjects in various studies ranged from 65.9 years to 76 years. Transdermal testosterone dosages ranged from 5 to 10 g/day, while intramuscular options were 125 mg/week or 200 mg every 2 weeks. Oral testosterone supplementation was given at 160 mg/day in one study. Pooled meta-analyses revealed greater muscle strength improvement after TRT compared with placebo (Hedges' g = 0.21; 95% CI: = 0.15-0.28). Intramuscular administration of TRT had greater efficacy (Hedges' g = 0.74; 95% CI: = 0.34-1.14) than transdermal and oral TRT (p < 0.001). A metaregression revealed that baseline serum total testosterone was associated with muscle strength improvement (ß = -0.004, p = 0.002). The risk ratios of adverse events, including elevated prostate-specific antigen, acute coronary syndrome, and prostate cancer, were not significantly different. CONCLUSION: TRT improved muscle strength in older, relatively hypogonadal men. The effect was more pronounced in populations with lower baseline testosterone levels.